The one that annoys me is the Sebille and Zaleskar conversation. There's no way that by the time you meet him normally you'll have levelled your Persuasion stat high enough to pass the check, and all of the other options result in combat; you can't even back out of the conversation once you've started it.
And as he's a pretty valuable vendor, I eventually just removed Sebille from the party and got someone else to talk to him so I could buy stuff. I think I'll go back and kill him once I've cleared up the rest of the island, or maybe even speak to him if I've scored some decent Persuasion gear by then.
This is my second play-through; I stopped my first play-through after getting to Jahan, as I had a better idea of how to play by then and wanted a more focussed party.
But I find it irritating that the respec mirror isn't available before finishing Fort Joy; it should be available from the get-go, as first time through, it's VERY easy to create a crappy party that will struggle in some of the harder fights.
It's also annoying that due to how slowly the game doles out skill points, you'll want to specialise each party member, but then end up in situations where even though another member of your party might have high Persuasion, the character you need to have it doesn't.
I'd even go so far as to say in the case of the above mentioned conversation, the game guides players to spec in such a fashion as to ensure almost everyone will fail it.
Reason for that thinking?
Sebille's default class is Rogue, and her background reinforces that idea (with possibly Shadowblade being an even better fit). That means the novice player will be inclined to spec her abilities in to Stealth and Thievery (the wiser player would avoid Stealth completely and stick to just Thievery, or even leave that to a completely different party member, such as Fane who doesn't need lockpicks, making for huge savings).
Then The Red Prince gets an inherent bonus to Persuasion, meaning it makes sense to make him the group's Persuasion specialist.
And who isn't going to take The Red Prince in their party?

All of which means that virtually nobody will spec multiple characters, let alone Sebille, in to Persuasion.
That's the kind of design decision that tempts me to whip out Cheat Engine, but I'm determined my first complete play-through will be cheat-free.
But I also understand that not all characters
should be able to pass all persuasion checks, and that this is a consequence of the player's levelling choices.
Second or third time around though?
Anything goes.